Synergistic Anti-Diabetic Effect of Green Synthesized Titanium Dioxide Nanoparticles and Metformin in STZ Induced Diabetes in Golden Hamster, Mesocricetus auratus
Herein, we synthesized titanium dioxide nanoparticles (TiO2NPs) using the cell-free filtrate of Xylaria feejeensis, an endophytic fungus of Andrographis paniculata, and tested their efficacy along with the diabetic drug metformin, in regulating streptozotocin (STZ)-induced diabetes in golden hamsters. Characterization of the TiO2 nanoparticles revealed an absorption peak at 280 nm, while SEM and TEM analyses showed diverse morphologies, including rod, spherical, triangular and mixed shapes. XRD and FTIR analyses established their anatase and rutile phases, including crystallite size and functional groups. Further, EDX confirmed the presence of titanium (55.82%) and oxygen (44.18%) atoms, while DLS (40–94) and zeta potential (-25.5 mV) indicated their size and stability. The in vitro study on the pancreatic beta-cell line MIN6 indicates that TiO2NPs can induce glucose-stimulated insulin secretion and inhibit the carbohydrate digestion enzymes α-amylase and α-glucosidase, thereby managing blood glucose levels. The lower doses of TiO2NPs induced the activity of SOD and decreased levels of lipid peroxidation in the golden hamster. Moreover, in vivo treatment with 10 mg/kg body weight dose of TiO2NPs showed a regenerative effect on the islets of Langerhans. It increases the number of immunoreactive insulin-producing beta-cells of the pancreas to counteract hyperglycemia in a STZ-induced diabetes model. However, co-treatment of TiO2NPs with metformin enhanced the efficacy of metformin, and overall, our observations suggest that use of TiO2NPs (10 mg/kg B.wt.) along with metformin (100 mg/kg B.wt.) can be a promising approach for better diabetic management. However, studies on efficacy and long-term safety issues need to be further validated.